Ebook Textbook of clinical embryology: Part 1

(BQ) Part 1 book Textbook of clinical embryology presents the following contents: Introduction to human embryology, reproductive system, cell division and gametogenesis, fertilization and formation of germ layers, extraembryonic membranes and twinning, integumentary system, skeletal system, muscular system,...

Clinical Embryology

Santosh University, Ghaziabad, NCR, Delhi.

Examiner in National and International Universities; Member, Academic Council, Santosh University;

Member, Editorial Board, Indian Journal of Otology; Vice President, Anatomical Society of India;

Medicolegal Advisor, ICPS, India; Consulting Editor, ABI,

North Carolina, USA

Formerly at: GSVM Medical College, Kanpur; King George Medical College, Lucknow;

Al-Arab Medical University, Benghazi (Libya);

All India Institute of Medical Sciences, New Delhi

ELSEVIER

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Reed Elsevier India Private Limited

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recording or otherwise, without the prior written permission of the publisher

ISBN: 978-81-312-3048-0

Medical knowledge is constantly changing As new information becomes available,

changes in treatment, procedures, equipment and the use of drugs become necessary

The authors, editors, contributors and the publisher have, as far as it is possible,

taken care to ensure that the information given in this text is accurate and up-to-date

However, readers are strongly advised to confirm that the information, especially with

regard to drug dose/usage, complies with current legislation and standards of practice

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My Parents

Textbook of Clinical Embryology has been carefully planned for the first year medical and dental students It follows

the revised anatomy curriculum of the Medical Council of India Following the current trends of clinically oriented

study of Anatomy, I have adopted a parallel approach of imparting basic embryological knowledge to students and

simultaneously providing them its applied aspects

To help students score high in examinations the text is written in simple language It is arranged in easily

under-standable small sections While embryological details of little clinical relevance, phylogenetic discussions, and

comparative analogies have been either omitted or described in brief, all clinically important topics are described in

detail Because of increasingly significant role of molecular biology and genetics in embryology and study of birth

defects, the basic molecular and genetic principles are discussed throughout the text In addition, a separate chapter

on medical genetics has been added The tables and flowcharts given in the book summarize important and complex

information into digestible knowledge capsules Multiple choice questions have been given chapter-by-chapter at

the end of the book to test the level of understanding and memory recall of the students The numerous simple

four-color illustrations and clinical photographs further assist in fast comprehension and retention of complicated

information All the illustrations are drawn by the author himself to ensure accuracy.

Throughout the preparation of this book one thing I have kept in mind is that thorough knowledge of embryology

is required by Clinicians, especially Gynecologists, Pediatricians, and Pediatric Surgeons for physical examination,

prenatal diagnostic tests, and surgical procedures Therefore, embryological events relevant to prenatal diagnostic

and surgical procedures are clinically correlated throughout the text Further, patient-oriented problems and their

embryological and genetic basis are presented at the end of each chapter for problem-based learning so that the

students could use their embryological knowledge in clinical situations Moreover, keeping in mind the relevance

of embryological knowledge in day-to-day clinical practice, a separate chapter on developmental events during

the entire period of gestation and their application in clinical practice is given at the end of the book

I pay my heartfelt tribute to all the authors of various embryology books, especially Developing Human: Clinically

Oriented Embryology, 8th edition by Keith L Moore and TVN Persaud, which I have consulted during the preparation

of this book From Developing Human and few other books, some photographs have been used in this book after

obtaining due permission from concerned authorities (please refer to page 331 for Figure Credits)

As a teacher, I have tried my best to make the book easy to understand and interesting to read For further

improve-ment of this book, I would greatly welcome comimprove-ments and suggestions from the readers All these comimprove-ments and

suggestions can be e-mailed at indiacontact@elsevier.com and drvishramsingh@gmail.com

‘Mind perceives new ideas best only when put to test.’

Vishram Singh

At the outset, I express my gratitude to Dr P Mahalingam, CMD; Dr Sharmila Anand, DMD; and Dr Ashwyn

Anand, CEO at Santosh University, Ghaziabad, NCR, Delhi for providing me an appropriate academic atmosphere

and encouragement which helped me a lot in preparing this book

I am highly grateful to Dr Devkinandan Sharma, Chancellor and Dr VK Arora, Vice Chancellor, Santosh University

for appreciating my work

I sincerely thank my colleagues in the Anatomy Department, Professor Nisha Kaul, Dr Latika Arora, Dr Ruchira

Sethi, and Dr LK Pandey for their cooperation, especially to Dr Ruchira Sethi for seeing the proofs sincerely

I highly appreciate the help rendered by my students Miss Radhika Batra and Mr Divyansh Bhatt and their

parents Dr Shailly Batra, Senior Gynecologist, Batra Hospital, New Delhi and Dr Arun Bhatt, Chief Medical

Superintendent, SGPGIMS Lucknow, respectively, who also happen to be my students and helped in procuring

some of the clinical photographs used in this book

I gratefully acknowledge the feedback and support of fellow colleagues in anatomy, particularly,

● Professors AK Srivastava (HOD), Ashok Sahai, PK Sharma, Mahdi Hasan, MS Siddiqui, and Punita Manik,

King George Medical College, Lucknow

● Professor NC Goel (HOD), Hind Institute of Medical Sciences, Barabanki

● Professors Shashi Wadhwa (HOD), Raj Mehra, and Ritu Sehgal, AIIMS, New Delhi; Gayatri Rath (HOD),

RK Suri, and Dr Hitendra Loh,Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi;

Shipra Paul and Shashi Raheja, Lady Harding Medical College, New Delhi; JM Kaul (HOD) and Smita Kakkar,

Maulana Azad Medical College, New Delhi; and Veena Bharihoke (HOD), UCMS, Shahadra, Delhi

● Professor GS Longia (HOD), People’s Dental Academy, Bhopal

● Professors AK Asthana (Dean) and Satyam Khare (HOD), Subharti Medical College, Meerut and Namita Mehrotra

(HOD), Rama Medical College, Hapur, Meerut

● Professor Vinod Kumar (HOD), UP RIMS & R Safai, Etawah, UP

● Professors Gajendra Singh (Director) and SK Pandey, Institute of Medical Sciences, BHU, Varanasi

● Professors RK Srivastava (HOD and Vice Principal), Rama Medical College, Kanpur

● Professors SL Jethani (HOD), RK Rohtagi, and Dr Deepa Singh, Himalayan Institute of Medical Sciences,

Jolly Grant, Dehradun

● Professor SD Joshi (HOD and Dean), Sri Aurobindo Institute of Medical Sciences; Dr VK Pandit, Associate

Professor, MGM Medical College; Professor GP Paul (HOD), Modern Dental College and Research Center,

Indore (MP)

● Professor Sudha Chhabra (HOD) and SK Srivastava, Medical College, Rohtak, Haryana

● Professor S Ghatak (HOD), Adesh Medical College, Bhatinda and Dr Anjali Jain (HOD), CMC, Ludhiana,

Punjab

● Professors TC Singel (HOD), MP Shah Medical College, Jamnagar and R Rathod (HOD), PDUMC, Rajkot,

Gujarat

● Professors P Parchand (HOD and Dean), GMC, Miraj; Ksheersagar Dilip Dattatraya, NKP Salve IMC & RC;

Meena Malikchand Meshram, GMC, Nagpur; Vasanti Arole and P Vatsalaswamy, DY Patil Medical College,

Pune, Maharashtra

● Professors Damayanti N (HOD), Regional Institute of Medical Sciences, Imphal; Manjari Chatterji, Medical

College, Calcutta and Kalyan Bhattacharya (HOD), Kalyani, West Bengal

● Professors PS Jevoor (HOD) and Daksha Dixit, JNMC, Belgaum, Karnataka

● Professor Kuldeep Singh Sood (HOD), Medical College, Budhera, Haryana

● Professor JK Das (HOD), Darbhanga Medical College, Bihar

● Dr Pradeep Bokatiya, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha

● Professors Dr Sundara Pandian (HOD) and SN Kazi, SRM Medical College, Potheri, Chennai

Lastly I eulogize the patience of my wife Mrs Manorama Rani Singh and my children Dr Rashi Singh and

Dr Gaurav Singh for not only happily tolerating my preoccupation but also helping me in preparation of the

manuscript

I gratefully acknowledge the help and cooperation received from the staff of Elsevier, a division of Reed Elsevier

India Pvt Ltd., especially Mr Vidhu Goel (Director, Clinical Education and Reference Division), Mrs Shabina Nasim

(Managing Editor), Mrs Shukti Mukherjee (Senior Commissioning Editor), Mrs Goldy Bhatnagar (Development

Editor), and Mrs Richa Srivastava and Mrs Shrayosee Dutta (Copy Editors) I highly appreciate the sincerity and

dedication of Mrs Shabina Nasim and Mrs Goldy Bhatnagar Lastly I would like to acknowledge the support of the

typesetter in bringing out the diagrams and text much to my satisfaction in a short time

Vishram Singh

Preface vii

5 Formation of Primitive Streak, Notochord, Neural Tube, Subdivisions of

Introduction to Human Embryology

1

Prenatal Development

The prenatal development is a fascinating and awesome

event It begins with a single cell—the zygote (fertilized

ovum) and culminates after 9 months (38 weeks or 266

days) with a complex organism—the newborn—made

of billion of cells This involves a process called

mor-phogenesis, which includes cell division,

transforma-tion or specializatransforma-tion, migratransforma-tion, and even programmed

cell death (apoptosis)

During morphogenesis, genetic or environmental

factors may affect the normal development of baby and

cause congenital anomalies

Thus embryology helps us not only in understanding

the rationale of structure and functions of each body

system but also in understanding the factors

responsi-ble for causing congenital anomalies The appreciation

of these factors may assist the clinicians in preventing

and treating such anomalies

Divisions of Prenatal Period

Clinically the prenatal period is divided into two parts:

(a) embryonic period and (b) fetal period

1 The embryonic period extends from fertilization

to the end of eight week and the developing

organ-ism is called an embryo The embryonic period is

further divided into two parts: (a) pre-embryonic

period and (b) embryonic period proper

2 The fetal period extends from beginning of the

ninth week (third month) until the birth

Overview

Embryology is the science that deals with development and

growth of an individual within the uterus (female genital tract)

It begins with fertilization of an ovum and culminates with the

birth of the baby The whole period of development from

fertiliza-tion to birth is termed prenatal development The development

of an individual continues even after birth up to age of 25 years

This period of development is termed postnatal development.

Embryologically the prenatal period is divided into three parts: (a) pre-embryonic period, (b) embryonic period, and (c) fetal period

1 Pre-embryonic period: It extends from

concep-tion (fertilizaconcep-tion) to the end of second week of intrauterine life (IUL) The morphogenic events during this period include fertilization, transporta-tion of zygote through the uterine tube, mitotic divisions/cleavage, implantation, and formation of primordial embryonic tissues

2 Embryonic period: It extends from beginning of

the third week to the end of eighth week of IUL

The morphogenic events during this period include differentiation of the germ layers into specific body organs and the formation of placenta, umbilical cord, and extraembryonic membranes

3 Fetal period: It extends from beginning of the

ninth week to birth During this period, there is tremendous growth and specialization of the body structures

The subdivisions of prenatal period and events ring in these periods are shown in Flowchart 1.1

occur-Postnatal Development

The postnatal development extends from birth to about

25 years The postnatal development is divided into following five parts/periods

1 Infancy (from birth to first year)

2 Childhood (from 2nd to 12th year)

3 Puberty (from 13th to 16th year)

4 Adolescence (from 17th to 18th year)

5 Adulthood (from 19th to 25th year)

Infancy

The infancy period extends from birth to 1 year and

newborn during this period is termed infant The

first four weeks of this period are very critical for the

survival of the newborn because the transition from

intrauterine to the extrauterine existence requires many

changes especially in the cardiovascular and respiratory

systems During this there is a rapid growth of the

body This period is called neonatal period and the

newborn during this period is termed neonate If

new-born survives first few hours after birth, his/her chances

of survival are usually good The care of baby during

the neonatal period is termed neonatology.

N.B The term ‘perinatal period’ used by clinicians extends from

28th week of pregnancy to the end of 6th day after birth.

Childhood

The period of childhood extends from beginning of the

second year to 12 years The care of children during this

period is exciting because of the constancy of change in

their growth and development The children do not

stay the same As the child grows the rate of growth

slows down; however, just before puberty the growth

accelerates It is called prepubertal growth spurt

The medical subject dealing with care of children in

health and disease is termed pediatrics.

Puberty (Latin: Pubertas, which means

development of sex characteristics)

The puberty period extends from 12 to 15 years in females

and 13 to 16 years in males During this period there is

a very rapid physical growth and development of

second-ary sexual characters During this period the capability of

sexual reproduction is attained The growth at puberty

is dependent upon the interaction of growth hormone

[insulin-like growth factor 1 (IGF-1)] and sex steroids

Adolescence

The adolescence period extends from 17 to 18 years

This period is characterized by rapid physical growth

and sexual maturation The gonads begin to secrete

testosterone and estrogen During this period the ity to reproduce is achieved

abil-Adulthood (Latin: Adultus, which means

grown up)

The adulthood period extends from 19 to 25 years

During this period full growth and development of body organs including ossification of bones is virtually completed

Subdivisions of Embryology General Embryology

It deals with the development of an individual during first eight weeks after fertilization (i.e., with pre-embryonic and embryonic periods) During this period a single cell called zygote (fertilized ovum) is converted into a form that externally resembles with the features of an adult individual and all organs and systems are formed

Systemic Embryology

It deals with the functional maturation of various organs and systems that are formed during the embry-onic period

(Conception to end of second week)

– Fertilization – Cleavage – Implantation – Formation of germ layers

(Beginning of third week to end of eighth week)

– Formation of placenta, umbilical cord, and extraembryonic membranes – Differentiation of germ layers into specific body organs

(Beginning of ninth week to birth)

– Growth and specialization of the body structures

Flowchart 1.1 Subdivisions of prenatal period and events occurring in these periods.

Chemical Embryology

It deals with the biochemical aspect of the prenatal

development

Teratology

It deals with abnormal embryonic and fetal

develop-ment It is a branch of embryology that is concerned

with the congenital anomalies or birth defects

Recent Advances in Embryology

1 Prenatal diagnosis: It is detection of congenital

abnormalities in an unborn child The various

techniques used for this purpose are:

(a) Amniocentesis

(b) Chorionic villous sampling

(c) Ultrasonography

(d) Fetoscopy

(e) Fetal blood sampling

(f) Maternal serum screening

(g) MRI, etc

2 In vitro fertilization: In vitro fertilization (IVF)

of human ova and embryo transfer in the uterus has

now become a standard procedure throughout the

world to solve the problems of infertility On 25th

July 1978, Louis Joy Brown, the first test tube

baby was born to Leslie Brown

3 Gene therapy: It deals with the replacement of a

deficient gene product or correction of an

abnor-mal gene It can be done in vitro or in vivo

4 Cloning: The advancement in molecular biology

has led to many sophisticated techniques that are

now widely used in research laboratories for genetic

regulation of morphogenesis Now the researchers

have started understanding how, when, and where

selected genes are activated and expressed in the

embryo during development For examples:

(a) Now cloning is possible The first mammal

clone, Dolly the sheep, was cloned in 1997

(Fig 1.1) by using the technique of somatic cell nuclear transfer

(b) The interest in human cloning has generated a

considerable debate because of social, moral, ethical, and legal implications

(c) More recently the cloning of a human embryo

was reported

5 Stem cell therapy: The stem cells are cells found in

multicellular organisms These cells have the

abil-ity to renew themselves and differentiate into a

diverse range of specialized cell types There are

two broad types of mammalian stem cells: (a)

Embryonic stem cells that are isolated from the inner

cell mass of the blastocysts (Fig 1.2) They are pluripotent, i.e., they have ability to form different cell types (b) Adult stem cells that are found in adult

tissues, e.g., bone marrow These cells are restricted

in their ability to form different cell types and therefore are multipotent, not pluripotent.

N.B The isolation and programmed culture of human embryonic stem cells hold a great potential for the treatment of degenerative, malignant, and genetic diseases (The embryonic stem cells are pluripotent They are capable of self-renewal and are able to dif- ferentiate into specialized cell types.) Ruth R Faden of Johns Hopkins University once said that we believe the obligation to relieve human suffering, which binds us all and justifies the instru- mental use in early embryonic life.

Utility and Scope of Embryology in Medicine

A thorough knowledge of embryology is important for following reasons

1 It explains the positions and relations of various organs and neurovascular structures in adult gross anatomy

Fig 1.1 Dolly, the sheep, the first cloned sheep.

Fig 1.2 Embryonic stem cells.

2 It helps to understand the cause of development of

various congenital anomalies such as

tracheoesopha-geal fistula, polycystic kidney, subhepatic cecum, etc

The knowledge of various factors causing genital anomalies (such as use of alcohol, smoking,

con-drugs, viral infections, teratogens, etc.) can be

use-ful in preventing their occurrence by rendering

advice and adopting preventive measures

3 Some aspects of general embryology such as

game-togenesis, fertilization, and implantation are of

great importance to understand the cause of

infer-tility and its management It also helps in family

planning

4 It forms the basis of concept of growth, repair, and

regeneration of tissues, and understanding of the

development of various embryonic tumors

5 Ex-utero surgery is now-a-days possible to treat

certain congenital anomalies, viz., congenital

dia-phragmatic hernias, repair of spina bifida, etc.,

only due to in-depth study of embryology

6 It provides the basis for medical termination of

pregnancy in various congenital diseases, which are

incompatible with life

7 It provides insight for use of molecular biology for

genetic regulation of human development

History of Embryology

The following text provides only a brief account of history of

embryology as a mark of respect to some legends who have a

significant contribution in the field of embryology.

‘If I have seen further, it is by standing on the shoulders

of the earlier giants.’

– Sir Issac Newton

1 Ancient Egyptians (3000 BC) knew about the

meth-ods of incubation of eggs of the birds They also believed

that the Sun god Aten is the creator of germ in woman

and seed in man, and gives life to the baby in the body

of mother.

2 The Garbha Upnishad, an ancient scripture of Hindus

(written in around 1416 BC), describes following ideas

about embryo:

(a) Embryo comes into existence from conjugation of

blood and semen during the period favorable for conception after sexual intercourse.

(b) Developmental stages of an embryo are as under:

● 1-day-old embryo Formation of Kalada

● After 7 nights Formation of vesicle

● After a month Formation of spherical mass

● After 2 months Formation of head

● After 3 months Formation of limbs

3 Hippocrates (460–377 BC) (Fig 1.3) gave the following

advice to understand the development of the embryo.

Take 20 or more eggs and let them be incubated by two

or more hens Then from the second day to the day of hatching remove one egg every day, break it, and exam- ine it You exactly see how embryo develops This devel- opment of chick embryo can be similar to that of man.

4 Aristotle (384–322 BC) (Fig 1.4) wrote a treatise on

embryology in which he described the development

of the chick and other embryos Aristotle is regarded

as the Founder of Embryology According to him embryo

develops from a formless mass, which he described as

a fully concocted seed with a nutritive soul and all body parts The mass arose from menstrual blood after activation by semen.

5 Claudeus Galen (130–201 AD) (Fig 1.5) wrote a book

on the formation of the fetus in which he described the

development and nutrition of fetuses He also described

structures that are now called allantois, amnion, and placenta.

6 Samuel-el-Yehudi (second century AD) described six

stages in the formation of embryo from a ‘formless, rolled-up thing’ to a ‘child whose months have been completed.’

7 The Quran (seventh century AD), the holy book of the

Muslims, describes that the human beings are produced from a mixture of secretions from the male and female

It also mentions that the human being is created from

nufla (small drop) It also states that the resulting

organism settles in the womb like a seed 6 days after its beginning The early embryo resembles a leech and later it resembles a ‘chewed substance.’

8 Leonardo da Vinci (1452–1519) (Fig 1.6) made

accurate drawings of dissections of uterus of pregnant women containing fetuses (Fig 1.7)

Fig 1.3 Hippocrates.

12 Caspar Friedrich Wolff (1759) proposed the layer cept, i.e., zygote produces layers from which the embryo

con-develops His ideas formed the basis of the theory of genesis, which states that the development results from

epi-growth and differentiation of specialized cells The mesonephros and mesonephric duct are called Wolffian body and Wolffian duct, respectively, after his name.

13 Lazaro Spallanzani said (1775) that both oocyte and

sperm are necessary for initiating the development of an individual.

14 Heinrich Christian Pander discovered the three germ layers in 1817.

Fig 1.4 Aristotle.

Fig 1.5 Claudius Galenus.

9 William Harvey (1578–1657) believed that male seeds

or sperms after entering the womb or uterus get

meta-morphosed into an egg-like substance that gives rise to

an embryo.

10 Regnier de Graaf was first to observe vesicular ovarian

follicles in 1672 with the help of simple microscopes,

which are still called Graafian follicles.

11 Johan Ham van Arnheim and Anton van

Leeuwenhoek were first to observe a human sperm

They thought that sperms contain a miniature preformed

human being that gets enlarged when sperm is

depos-ited in the female genital tract.

Other embryologists at this time thought that the

oocyte contained a miniature human being that enlarged

when it was stimulated by a sperm (Fig 1.8).

Fig 1.6 Leonardo da Vinci.

Fig 1.7 Reproduction of Leonardo da Vinci’s drawing made

in the 15th century AD to show a fetus in the uterus.

15 Etienne Saint Hilaire and Isidore Saint Hilaire made

the significant studies of abnormal development in

1818, initiating what we now know as the science of

teratology.

16 Karl Ernst von Baer (Fig 1.9) described the oocyte in

the ovarian follicle of the dog in 1827 He also noted

cleaving zygote in uterine tube and blastocysts in the

uterus They provided new knowledge about the origin

of tissues and organs from three germ layers of the

embryo that formulated two embryological concepts:

(a) corresponding stages of embryonic development and (b) that

general characteristics precede specific ones For his

signifi-cant and far-reaching contributions he is regarded as the

Father of Modern Embryology.

17 Hans Spemann (1869–1941) discovered the

phenom-enon of primary induction, i.e., how one tissue determines

the fate of another He was awarded Nobel Prize in 1935.

18 Patrick Steptoe and Robert G Edwards (Fig 1.10)

pioneered the development of the technique of in vitro

fertilization The Louise Brown is the first ‘test tube baby’

born in 1978.

19 James Till (1931–) (Fig 1.11) along with Ernest

McCulloch discovered stem cells in 1960 Since the

discovery of stem cells by James Till, the hope for

treat-ment of terminal diseases has become enormous.

20 Ian Wilmut (1944), an English embryologist (Fig

1.12), is best known for leading a team that cloned a

mammal from an adult somatic cell in 1996—a Finnish

Dorset lamb named Dolly (Fig 1.1) The cloning is a

cell, cell product, or organism that is genetically identical

to the unit or individual from which it was derived

Clones are duplicates of each other resembling in

anat-omy and physiology.

Embryological Terms

Most of the terms used in embryology are of Latin (L.) or Greek (Gr.) origin Following text deals only with those

terms that are commonly used.

1 Oocyte (L Ovum = egg): Female germ or sex cells duced by ovaries.

2 Sperm (Gr Sperma = seed): Male germ cells produced

by testes.

3 Zygote: Cell formed by union of a sperm and secondary

oocyte (ovum) The zygote is the earliest stage of embryo (i.e., the beginning of the new human being).

4 Conceptus: Product of conception, i.e., embryo along

with its extraembryonic membranes.

5 Cleavage: Series of mitotic divisions of the zygote to

form early embryonic cells—the blastomeres.

6 Morula (L Morus = mulberry): Solid ball of 12–32 cells (blastomeres) formed 3–4 days after fertilization, just at the time when embryo enters the uterus.

Fig 1.8 Seventeenth century drawing of a sperm by Hartsoeker.

Fig 1.9 Karl Ernst von Baer.

Fig 1.10 Patrick Steptoe.

7 Blastocyst (Gr Blastos = bud, Kystis = bladder): It

forms at late morula stage when fluid passes into

inter-cellular spaces between the inner and outer layers of

cells and forms a fluid-filled cavity The blastocyst is

divided into two parts: an outer layer of small, slightly

flattened cells called trophoblasts and inner cell mass

Fig 1.11 James Till.

Fig 1.12 Ian Wilmut.

(embryoblast) consisting of a group of larger polyhedral cells.

The cavity of blastocyst (blastocele) separates the phoblast from the inner cell mass except for a small area where they are in contact.

8 Implantation: Attachment and subsequent embedding

of blastocyst into uterine endometrium, where it ops during gestation Implantation occurs between fifth and seventh day after fertilization.

9 Gastrulation: Formation of three germ layers (ectoderm,

mesoderm, and endoderm) in the embryo It is the most characteristic event during the third week of gestation.

10 Neurulation (Gr Neuron = nerve): Process by which neural plate forms the neural tube.

11 Embryo (Gr Embryon): Developing human from

con-ception to eighth week in uterus This period is called embryonic period (or period of organogenesis) By the end of this period primordia of all the major structures

of the body are formed.

12 Primordium (L Primus = first + Ordior = to begin):

Beginning or first discernible indication of an organ or structure.

13 Fetus (L Unborn = offspring): Developing human from ninth week to birth During this period (fetal period), differentiation and growth of the tissues and organs formed during the embryonic period takes place.

14 Abortion (L Aboriri = to miscarry): Expulsion of a ceptus (embryo or fetus) before it is unable, i.e., capable

con-of living outside the uterus.

15 Gestation (L Gestatio = bearing, carrying in the womb):

The duration of embryo in the uterus from fertilization

of the ovum until delivery (the period of normal pregnancy).

16 Gestational age: The gestational age of embryo/fetus is

calculated from presumed first day of the last normal menstrual period The oocyte is not fertilized until approximately 14 days (2 weeks after the preceding men- struation); hence the fertilization age of an embryo or fetus

is 14 days less than the gestation age.

GOLDEN FACTS TO REMEMBER

 Father of modern embryology Karl Ernst von Baer

 First individuals to observe human sperm Johan Ham van Arnheim and Anton van Leeuwenhoek

 Carnegie collection of embryo is now in National Museum of Health and Medicine in the Armed Forces

Institute of Pathology in Washington DC

CLINICAL PROBLEMS

1 How do the terms zygote and conceptus differ?

2 What do you understand by the term teratology?

3 What are stem cells? Which are the diseases that are likely to be benefited by the stem cells?

CLINICAL PROBLEM SOLUTIONS

1 The zygote is a diploid single cell formed after fertilization by the union of haploid male and female gametes.

The term conceptus refers to the product of conception, i.e., embryo and its extraembryonic membranes.

2 This is the branch of embryology that deals with the congenital anomalies and defects.

3 The cells of embryoblast are capable of generating all the three germ layers, viz., ectoderm, mesoderm, and

endo-derm Hence cells of embryoblast (inner cell mass) are termed embryonic stem cells They can be kept in an ferentiated state in culture medium By using growth factors they can be made to form different tissue cells, e.g., muscle cells, neurons, blood cells, etc The diseases that are likely to be benefited by stem cells are Parkinson’s disease, Alzheimer disease, spinal cord injury, etc.

undif- First mammal cloned Dolly, the female domestic sheep (5th July 1996–14th February

2003)

 Inventor of first mammal cloning Ian Wilmut (1944)

 Most famous siamese twins Chang and Eng Bunker (born in 1811 in Siam Thailand)

 Discoverer of stem cells James Till (1931–)

 Stem cells were discovered in 1960 by James Till

 Longest period of prenatal development Fetal period

 Earliest period of extrauterine life Infancy (first year after birth)

Male Reproductive System

Overview

The primary reproductive organ in male is testis The

second-ary reproductive organs in male are scrotum, epididymis,

ductus deferens, seminal vesicles, urethra, prostate gland,

bul-bourethral glands, and penis (Fig 2.1) The male genital tract

consists of vasa efferentia (efferent ductules), epididymis, vas

deferens, ejaculatory duct, and urethra The male genital tract

carries the sperms produced in the testis to the urethra, from

where they are deposited in the vagina during copulation

(intercourse).

Testes

These are a pair of ovoid organs within the scrotum that

produce sperms and testosterone Each one is 4–5 cm

long lying within the scrotum Each testis is suspended

in the scrotum by the spermatic cord Spermatic cord

provides vascular, lymphatic, and nerve supply to the

tes-tes, and provides passage to the vas deferens The outer

part of each testis is made of thick, white capsule—the

tunica albuginea (Fig 2.2) The fibrous septum from the capsule extends inside and divides each testis into 200–300 cone-shaped lobules Each lobule contains

one to three convoluted seminiferous tubules The

epithelial lining of their walls contains cells that develop into spermatozoa by a process of cell division Surrounding

the tubules are interstitial cells of Leydig, which secrete male hormone—the testosterone.

The seminiferous tubules empty their secretion (e.g.,

spermatozoa) into tubular network—the rete testis that in turn empty into 15–20 efferent ductules The

efferent ductules enter into the epididymis to form the

duct of epididymis.

Epididymis

It is a comma-shaped structure lying posteriorly and slightly lateral to each testis with vas deferens along its medial side The epididymis consists of a single convo-

luted duct (duct of epididymis) formed by the union

of the efferent ductules of the testis Within the duct

of epididymis the spermatozoa mature, develop some motility, and learn a little bit of swimming They show circular or even forward directional movements

Ampulla of vas deferens Urinary bladder

Seminal vesicle Ejaculatory duct Bulbourethral gland (Cowper’s glands) Penis

Duct of epididymis

Testis

Scrotum

Vasa efferentia (efferent ductules of testis) Vas deferens

Prostate Urinary bladder

Fig 2.1 Male reproductive system.

Reproductive System

2

Vas Deferens

It is a thick-walled muscular tube, about 45 cm (18

inches) long, which begins at the tail of the epididymis

as the direct continuation of the duct of the epididymis

It runs upward along with vessels within the spermatic

cord The terminal part of each vas deferens is sacculated

and called ampulla of vas deferens It serves as a

reser-voir of sperm and tubular fluid The terminal narrow part

of vas deferens joins the duct of seminal vesicle to form

the ejaculatory duct at the base of the prostate gland

Main function of vas deferens is to transport spermatozoa from

the epididymis to ejaculatory duct Peristaltic contractions

of smooth muscle help in propelling the semen The vas

deferens is cord like when grasped between thumb and

index finger because of its thick wall and small lumen

Seminal Vesicles and Ejaculatory Ducts

The seminal vesicle (5 cm long) is a sacculated coiled

tube adjacent to ampulla of each vas deferens The

paired seminal vesicles secrete a major portion of

vol-ume of ejaculate These are located behind the bladder

near the prostate gland Each vesicle ends in a small

duct that joins ampulla of vas deferens to form an

ejacu-latory duct Two ejacuejacu-latory ducts are slender tubes

that open into the prostatic part of the urethra The

secretion of seminal vesicles is thick and mucous like It

contains fructose that provides nutrition to sperms

Prostate Gland

It is a pyramidal fibromuscular gland of about the size

of a chestnut It is gray to reddish in color It consists

mainly of glandular and muscular tissue

The prostate gland surrounds the proximal part of the urethra and two ejaculatory ducts Gland is enclosed

by a thin but strong fibrous capsule The capsule is tinuous with several fibromuscular partitions The

con-prostatic glands secrete the con-prostatic fluid, which is

poured into the prostatic urethra through 10–20 ducts

The prostatic fluid contains acid phosphatase, sin, citric acid, amylase, prostate specific antigen, and prostaglandins The prostatic fluid forms the bulk of the semen (i.e., ejaculate)

fibrinoly-Bulbourethral Glands (Cowper’s Glands)

These are two yellow, pea-sized glands located one on each side of membranous urethra These glands secrete alkaline mucus that is poured into the penile urethra just before ejaculation of the semen The secretion of these glands mixes with sperms and other glandular secretions to form semen They contribute 5–6% of total ejaculate Alkalinity of their secretion protects sperms against the acidity of the urethra and vagina

The secretions of bulbourethral glands also provide lubrication during coitus

Penis

It is the male organ of copulation It is pendulous and visibly consists of glans penis and shaft of penis Two of erectile columns forming the dorsal portion and the sides of penis are called corpora cavernosa The third erectile column forming the ventral portion of penis is termed corpus spongiosum The distal end of corpus spongiosum expands to form a triangular enlargement

called glans penis Urethra travels through the corpus

Lobules of epididymis

Efferent ductules (15–20 in number) Duct of epididymis

Rete testis

Fibrous septa

Convoluted seminiferous tubules (2–3 in each lobule)

Tunica albuginea

Lobules of testis (200–300)

Vas deferens

Fig 2.2 Schematic vertical section of the testis to show the basic structure of testis, epididymis, and vas deferens.

spongiosum and opens as external urethral orifice on

the tip of glans penis

N.B Semen: It is the fluid ejaculated into the vagina at the time

of orgasm It consists of sperms produced by seminiferous tubules

of testes and secretion of seminal vesicles, prostate, and

bulboure-thral glands The average volume of ejaculate is 2.5–3.5 ml Semen

has a pH of 7.35–7.5 with average sperm count of 100 million

per ml It is white and opalescent The approximate contribution by

various reproductive glands is as under:

• Seminal vesicles: 60%

• Prostate: 30%

• Testes: 5%

• Bulbourethral glands: 5%

Thin milky secretion of the prostate gland is alkaline in nature and

neutralizes the acidic pH of the vagina The movement of sperms is

best at pH of 6–6.5 while vaginal pH is about 3.5–4.

The enzymes of prostatic secretion break down the coagulated

proteins secreted by seminal vesicles and make the semen more

liquid.

Female Reproductive Organs

Overview

The primary reproductive organ in the female is ovary The

sec-ondary reproductive organs in the female are uterine tubes,

uterus, vagina, vulva, and vestibular glands The female genital

tract consists of fallopian tube, uterus, and vagina (Fig 2.3) The

female genital tract provides the site of fertilization and site for

the development of the embryo.

Ovaries

These are a pair of small ovoid organs (3 cm long × 2 cm wide × 1 cm thick) of about the size and shape of an almond They are situated in the lateral wall of the lesser pelvis on either side of the uterus below and behind the uterine tubes Each ovary is attached to the upper part of the uterus by the round ligament of the ovary

One end of the ovary is in contact with the fimbria of the uterine tube

The ovary consists of a thick cortex surrounding a very vascular medulla The cortex surrounding the medulla consists of a framework of connective tissue

covered by the germinal epithelium Before puberty, it contains numerous primordial follicles After puberty,

it contains ovarian follicles in various stages of rity Each one of them contains an ovum Till puberty the ovaries remain inactive but stroma still contains immature follicles

matu-During childbearing age, one ovarian follicle matures and ruptures to release its ovum into the peritoneal

cavity This process is called ovulation and recurs (ovarian cycle) throughout the reproductive life of the

female If the woman becomes pregnant, the ovarian cycle stops temporarily

Ovarian Cycle (Figs 2.4 and 2.5) The ovarian cycle is the cyclic release of ovum from the

ovary This cycle is controlled by hormones secreted by the pituitary gland At the onset of puberty, the pituitary

Round ligament

of ovary

Ovary

Perimetrium Myometrium Endometrium

Vagina

Uterine cavity

Fimbria of uterine tube

Intramural part Isthmus

Ampulla Infundibulum Parts of uterine tube

Fig 2.3 Female reproductive system.

gland secretes follicle stimulating hormone (FSH)

Under the influence of this hormone, the primordial

follicles in the ovary start growing The growing/

maturing follicles produce the hormone estrogen

Only one follicle reaches the full development and

forms Graafian follicle By the feedback mechanism,

the increased level of estrogen hormone inhibits the

secretion of FSH from the anterior pituitary The

pitu-itary gland also secretes luteinizing hormone (LH)

Under the influence of a large amount of LH, the Graafian follicle bursts and ovulation takes place The ovum is released due to action of proteolytic enzymes formed by the theca externa cells that cause dissolution

of capsular wall There is plasma transudation within the follicles As a result, they swell and pressure within them increases Due to increased intrafollicular pres-sure and simultaneous dissolution of follicular capsular wall, the follicle ruptures and ovum is released (ovula-tion) After ovulation, the empty follicle develops into

corpus luteum that secretes hormone progesterone

The corpus luteum degenerates after 10 days if the ovum is not fertilized The level of progesterone decreases, and again the pituitary secretes FSH and a

new cycle starts Thus, the cyclic changes in the

ovary comprising of development of ovarian cles, ovulation, and formation of corpus luteum constitute the ovarian cycle.

folli-The corpus luteum persists for 2–3 months if the ovum is fertilized By that time placenta develops and starts secreting progesterone and estrogen The high levels of these hormones in blood further suspends the ovarian cycle during pregnancy

N.B The ovarian cycles normally persist throughout the ductive life of women except during pregnancy The ovarian cycle terminates at menopause.

repro-Germinal epithelium Cortex

Ovulation

Secondary oocyte

Graafian follicle

Corpus luteum Corpus

albicans

Primary follicles

Oocyte

Maturing secondary follicle

Secondary follicle

Mesovarium Primordial follicle

LUTEAL PHASE

FOLLICULAR PHASE

Medulla

Fig 2.4 Schematic diagram of ovary showing various stages of development of ovarian follicles, and formation of corpus luteum

and corpus albicans.

Adenohypophysis

Pituitary gland

Growth of follicles Ovulation

Formation of corpus luteum

Progesterone Estrogen

−

Fig 2.5 Ovarian cycle.

The uterus consists of three layers From superficial

to deep these are perimetrium, myometrium, and endometrium

1 Perimetrium: It consists of peritoneum covering

the uterus

2 Myometrium: It is the thickest layer and consists

of smooth muscle The smooth muscle fibers are arranged in longitudinal, oblique, transverse, and circular layers Hence the wall of the uterus is very strong During pregnancy, the muscle fibers undergo

hyperplasia and hypertrophy This layer contains

blood vessels and nerves; hence it is also called

stratum vasculare.

3 Endometrium: It is the mucous lining of the body

of the uterus containing a large number of secreting glands

The endometrium consists of following three layers (Fig 2.7) From outside to inside these are:

(a) Stratum basale/basal layer: It is thin and has a

separate blood supply

(b) Striatum spongiosum/spongy layer: It is thick and

edematous

(c) Stratum compactum/compact layer: It is thin and

superficial towards the uterine lumen It consists

of compactly arranged stromal cells

Mnemonic: BSC = Basal layer; Spongy layer;

Compact layer

N.B The compact and spongy layers together form stratum

functionalis (functional layer), which is sloughed off during

men-struation The basal layer is never sloughed off.

Two phases of the ovarian cycle: The ovarian cycle is

divided into two phases: (a) follicular phase and

(b) luteal phase

1 The follicular phase corresponds to the first half of

the menstrual cycle During this phase follicles develop

and discharge only one mature oocyte

Changes in the endometrium of uterus take place

due to secretion of the hormone estrogen produced

by the developing follicles

2 The luteal phase corresponds to the second half of

the menstrual cycle During this phase, there is

for-mation of the corpus luteum following ovulation

Changes in uterine endometrium take place due to

secretion of the hormone progesterone.

Uterus (Fig 2.6)

It is a hollow, thick-walled muscular organ where fetus

develops It is a pear-shaped organ, which is flattened

anteroposteriorly It lies in anteverted and anteflexed

position in the lesser pelvis

It is about 7.5 cm long, 5 cm wide, and its walls are

about 2.5 cm thick It weighs about 30–40 g

It has three parts: fundus, body, and cervix

● Fundus is the upper dome-shaped part of the uterus

above the openings of uterine tubes It is devoid of

cavity

● Body is the main part of the uterus where fetus

develops

● Cervix is the lower cylindrical part of the uterus that

protrudes into the vagina

Body

Fundus

Fundus

Uterine tube

Uterine cavity

Uterine wall

Internal os Cervical canal

External os Cavity of vagina

Body Isthmus Supravaginal portion of cervix Vaginal portion of cervix Cervix

Vagina

Fig 2.6 Uterus A External view B Internal view.

Menstrual Cycle (Fig 2.8)

The uterine endometrium undergoes monthly cyclic

changes during reproductive life of a woman called

endometrial cycle, which is commonly referred to as

the menstrual cycle because of menstruation (flow of

blood from the uterus) as a notable feature At the age of

45 years, the menstruation ceases and this stage is termed

menopause (cf Similar cyclic changes occur in

ova-ries, which constitute the ovarian cycle, see page 11.)

Each menstrual cycle in most of the women consists

of roughly 28 days Day 1 is the day when the

men-strual flow starts The ovulation occurs in the middle of

the cycle (i.e., 14th day)

Each menstrual cycle is divided into four phases on

the basis of changes that occur in the endometrium

The phases are:

1 Menstrual phase

2 Proliferative phase

3 Secretary phase

4 Premenstrual phase

N.B Changes in the endometrium occur as a result of hormones

(estrogen and progesterone) secreted by the ovaries (ovarian

cycle), which in turn is controlled by the hormones secreted by the

hypothalamus and pituitary gland.

1 Menstrual phase (menses) (1–4 days): If the ovum

is not fertilized, the corpus luteum degenerates;

and level of progesterone drops down The coiled

endometrial arteries undergo spasm The blood

supply to the spongy and compact layers of the

endometrium is reduced The functional layer

undergoes necrosis and sloughed off, and there is

hemorrhage from the stumps of the endometrial

arteries The sloughing continues until only raw surface of the stratum basale is left

N.B It takes about 14 days after ovulation in breaking down the spongy and compact layers of endometrium Note the basal layer of endometrium remains intact.

If the ovum is fertilized, first the corpus luteum and then the placenta continue to secrete proges-

terone, and the menstrual cycle remains suspended during pregnancy

2 Proliferative phase/follicular phase (5–14 days):

The proliferative phase coincides with the tion of the estrogen by the maturing follicles of the ovary

3 Secretory phase/luteal phase (15–25 days): The

secretory phase coincides with the secretion of gesterone by the corpus luteum

4 Premenstrual phase (26–28 days): The females,

usually the younger ones, often complain of severe spasmodic pain and external spotting of blood during this phase due to ischemia of the uterine wall following drop in the level of progesterone hormone

1 Abnormal menstrual cycles

(a) Hypomenorrhea: It is scanty blood flow during the

men-strual cycle.

(b) Menorrhagia: It is profuse blood flow during the

men-strual cycle.

(c) Metrorrhagia: It is the occurrence of bleeding between

the menstrual cycles.

(d) Oligomenorrhea: It is reduced frequency of menstrual

cycles.

Clinical Correlation

Lining epithelium (simple, columnar, and secretory)

Stratum compactum

Stratum spongiosum

Stratum basale Myometrium

Uterine gland Spiral artery

Straight artery

Fig 2.7 Layers of endometrium.

2 Amenorrhea: It is the absence of menstruation Amenorrhea

may be of two types: primary and secondary.

(a) Primary amenorrhea: It is the condition when menstrual

bleeding does not occur after 16 years of age.

(b) Secondary amenorrhea: It is stoppage of menstrual cycles

with normally occurring menstrual cycles before Most common cause of amenorrhea is pregnancy.

The features of different phases of menstrual cycle are

summarized in Table 2.1

N.B The menstrual cycle is a continuous process, and each phase

gradually passes into the next one.

Hormonal Control of Menstrual Cycle

(Fig 2.9)

The menstrual cycle is controlled by the hormonal

secretions of hypothalamus, adenohypophysis, and ovary

3 The FSH causes maturation of one or more ovarian

follicles The secondary follicle is converted into the Graafian follicle.

4 The granulosa cells of the secondary and Graafian

follicles secrete estrogen.

Primordial follicle

Primary follicle

1–4 days

Menstrual phase

15–25 days

Secretory phase

26–28 days

Premenstrual phase

Secondary follicle

Follicular phase

Graafian follicle

Corpus luteum

Corpus albicans Ovulation

14th day

Luteal phase

Stratum compactum

Stratum spongiosum Stratum basale

Fig 2.8 Correlation between ovarian and menstrual cycles.

Table 2.1 Features of different phases of the menstrual

cycle

Menstrual phase (1–4 days)

Necrosis and shedding of the functional layer of the endometrium associated with bleeding

Proliferative phase (5–14 days)

Regeneration of the functional layer

of the endometrium Secretory phase

(15–25 days)

Endometrium becomes thick and soft due to increased secretory activity of endometrial glands

Premenstrual phase (26–28 days)

Ischemia of endometrium due to reduced blood supply Cramping or pain and external spotting of blood

5 The estrogen stimulates the uterine endometrium

to enter the proliferative phase (the level of

estro-gen rises to a peak just before the LH surge)

6 The LH surge stimulates ovulation

7 Following ovulation, the lutein cells of the corpus

luteum secretes progesterone.

8 The progesterone stimulates the uterine

endome-trium to enter the secretary phase

N.B The hormones secreted by hypothalamus, adenohypophysis,

and ovary prepare the endometrium of the uterus for implantation

of the conceptus (blastocyst) If fertilization does not occur, the

granulosa cells produce inhibin, a protein that acts on

adenohy-pophysis and inhibits the secretion of gonadotrophins, which leads

to the regression of corpus luteum The endometrium undergoes

ischemic necrosis due to decrease in the level of progesterone and

estrogen, especially progesterone secretion by the degenerating

corpus luteum.

For details see Chapter 3

The ovarian and menstrual cycles go on

hand-in-hand throughout the reproductive life of women except

during pregnancy These cycles terminate at

meno-pause usually between the ages of 45 and 55 years.

N.B Correlation between ovarian and menstrual cycles: The

ovarian and menstrual cycles run parallel to each other Both of

these cycles are of 28 days duration.

In fact, the menstrual cycle is dependent on the ovarian cycle because the uterine endometrium undergoes cyclic changes under the influence of hormones secreted by the developing ovarian fol- licles and corpus luteum of the ovary.

Use of hormones in birth control (contraceptive) pills: The

sex hormone estrogen with or without progesterone is used in the preparation of contraceptive pills These hormones in con- traceptive pills act on the hypothalamus and pituitary gland resulting in inhibition of secretion of GnRH, and FSH and LH,

the secretion of which is essential for ovulation to occur The suppression of ovulation is the basis for the contraceptive pills.

The most common variety of the contraceptive pill

distrib-uted by the government of India contains progestin terone acetate) 1 mg and estrogen (estradiol) 50 μg These pills are distributed in packets with each packet containing 28 pills

(norethis-Out of which 21 pills contain these hormones and 7 pills do not contain hormones The woman is asked to start taking these pills

5 days after the onset of menstruation and continue without any break as long as pregnancy is not desired Normal menstru- ation occurs during 7 days in which she takes pills without hor- mone If the contraceptive pills are taken on a regular basis, the menstrual cycles occur regularly, each with 28 days As she

Menstrual phase

Proliferative phase

Secretory phase Premenstrual phase

Fig 2.9 Hormonal control of the menstrual cycle.

starts taking pills without hormones after 21 days, the

with-drawal of hormone induces menstruation after 2 days.

Sperm Transport (Fig 2.10)

During coitus (sexual intercourse) about 200–600

mil-lion sperms are deposited around the external os of the

cervix and in the fornices of the vagina The following

factors are responsible for passage of sperms from the

uterus to uterine tubes:

1 Muscular contractions of the walls of the uterus

and fallopian tube (main factor) The

prostaglan-dins of semen are thought to stimulate uterine

contractions at the sexual intercourse

2 Movements of the sperms: The fructose secreted by

the seminal glands provides energy to sperms

N.B Only about 200 sperms reach the fertilization site

Most of them degenerate and are absorbed by the female genital tract.

Oocyte Transport (Fig 2.10)

During ovulation, the fimbriated end of the fallopian tube becomes closely applied to the surface of the ovary and the finger-like fimbriae start moving back and

forth (sweeping action) over the ovarian surface The

sweeping action of fimbriae and fluid currents duced by cilia of the mucous lining of fimbria sweeps the ovum (secondary oocyte) into the infundibulum of the uterine tube as soon as it is discharged from the ovarian follicle

pro-From infundibulum, the oocyte passes to the ampulla

of the tube mainly by the peristaltic movements of the tubal wall

GOLDEN FACTS TO REMEMBER

 Total number of seminiferous tubules in each testis 400–600

 Most important function of testis (a) Formation of sperms

(b) Production of testosterone hormone

 Reproductive period of woman’s life Period in which she can bear children

 Most important event of the ovarian cycle Ovulation

Uterine cavity

Ovary

Cervical canal

External os Sperm

Sperm

Ampulla of uterine tube

Ovum (secondary oocyte) Uterine tube

Site of fertilization

Fig 2.10 Transport of sperms and ovum to the site of fertilization.

CLINICAL PROBLEMS

1 Why male fertility is evaluated first when an infertile (childless) couple visits a doctor, by advising semen

analysis?

2 What are the causes of male infertility?

3 What is the most effective permanent method of contraception in males?

4 In some women cause of infertility is anovulation (i.e., cessation of ovulation) Is it possible to induce ovulation in

these women?

5 How ovulation is assessed clinically?

6 What is the importance of determining the time of ovulation?

7 Which is most precarious time of prenatal development? Give the embryological basis.

CLINICAL PROBLEM SOLUTIONS

1 This is because the semen analysis is easier to perform The average volume of semen ejaculated in the vagina

dur-ing sexual intercourse is 2–6 ml (average 3.5 ml) There are usually more than 100 million sperms per ml of semen

of normal males A man with less than 10 million sperms per ml of semen is likely to be sterile, especially when the specimen contains immotile and abnormal sperms.

2 The common causes of male infertility are low sperm count (oligospermia), poor sperm motility, abnormal sperms,

and obstruction of the genital tract (e.g., vas deferens), etc.

3 The most effective permanent method of contraception in males is ‘vasectomy.’ This procedure involves the

exci-sion of a segment of each ductus (vas) deferens Following vasectomy there are no sperms in the semen or late, but the volume remains the same.

ejacu-4 Some women do not ovulate due to inadequate secretion of FSH and LH The ovulation can be induced in these

women by the administration of gonadotrophins or an ovulatory agent such as clomiphene citrate By competing

with estrogen for binding sites in the adenohypophysis, the clomiphene citrate suppresses the normal negative feedback loop of estrogen on the adenohypophysis This in turn stimulates the release of pituitary gonadotrophins (FSH and LH) secretion, which causes maturation of several ovarian follicles and thus induces ovulation.

5 The ovulation is accompanied by:

(a) A variable amount of abdominal pain in some women because ovulation results in slight bleeding in the toneal cavity.

peri-(b) A slight drop in the basal body temperature.

of age)

 Most important feature of menstrual cycle Monthly flow of blood per vaginum

 Most important factor to initiate menstruation Withdrawal of estrogen and progesterone hormones

 Most common cause of amenorrhea

(i.e., absence of menstruation)

Pregnancy

In a 28-day menstrual cycle, the ovulation takes place at about the middle of the cycle, to be exact on day 14 before the start of next menstrual bleeding.

There are many methods to find out the exact time of ovulation, but the one that is easy and commonly used

is a temperature method In this method, woman’s body temperature is recorded every morning before getting up

and plotted on a graph The temperature is low during menstruation, subsequently it rises, and at about the middle

of the cycle it suddenly falls to rise again The rise in temperature after sudden fall indicates that ovulation has occurred.

Following ovulation basal body temperature increases by 0.3–0.5°C.

6 The importance of determining the time of ovulation is twofold:

(a) Rhythm method of family planning (i.e., pregnancy is not desired): After ovulation, the ovum remains viable only

for 2 days and sperms deposited in vagina remain viable only for 4 days Therefore, fertilization can occur only

if intercourse is done 4 days before ovulation to 2 days after the ovulation Barring these 6 days, the remaining

days of the menstrual cycle are regarded as safe period Thus pregnancy can be avoided if intercourse is done

during safe period.

(b) Achievement of pregnancy (i.e., pregnancy is desired): In case of infertility (failure to conceive), the couples are

advised to have sexual intercourse during the unsafe period (i.e., 4 days before ovulation to 2 days after the ovulation) because this period is most favorable for conception.

7 The most precarious time of prenatal development is during the embryonic period (i.e., from the beginning of the

third week to the end of the eighth week) This is because there is much tissue differentiation and organ formation during this period Mostly, however, a woman does not realize that she is pregnant until it is very late Therefore, a woman should consistently take care of herself and abstain from taking certain drugs including antibiotics (espe- cially during 14 days before next menstruation) even if there is a remote chance that she is pregnant or might become pregnant in the near future.

Cell Division and Gametogenesis

The body is essentially a cellular structure and begins its

exis-tence as a single cell—the zygote It develops by multiplication

and differentiation of cells It matures as the cells and

sub-stance secreted by them achieve the mature state The

senes-cence (i.e., beginning of old age) and death pursues as a result of

decay and cessation of the cellular activities The human body is

made up of 60–100 trillion of cells The body cells are broadly

divided into two types: somatic cells and germ cells The

somatic cells are essential for growth, development,

regenera-tion, and maintenance of various tissues of the body, whereas

germ cells are essential for the production of gametes.

The life begins as a single cell—the zygote (vide supra)—formed

by union of male and female gametes or germ cells In humans,

the male gametes are spermatozoa or sperms, which are

pro-duced by testis from puberty onward The female gametes are

secondary oocytes, which are released from ovary in a cyclic

fashion throughout the reproductive life of a female.

The gametes are specialized cells for reproduction Each

gamete cell has a haploid (half) number of chromosomes (i.e.,

23 chromosomes) Each body cell (somatic cell) has diploid

(double) number of chromosomes (i.e., 46 chromosomes) The

46 chromosomes are arranged in 23 pairs The 22 pairs of these

chromosomes are called autosomes whereas the 23rd pair is

called sex chromosomes The sex chromosomes are of two types:

X and Y Females have two X chromosomes while males have one

X and one Y chromosome Conventionally this is expressed as a

formula 44XX in females and 44XY in males

Each gamete has only 23 chromosomes In females, secondary

oocytes are of only one type, i.e., each secondary oocyte has

22 autosomes and one X chromosome (22X) In males, there

are two types of sperms—one containing X (22X) and the other

containing Y (22Y) The sperm containing X chromosomes is

called X-bearing sperm or gynosperm and sperm containing

Y chromosomes is called Y-bearing sperm or androsperm.

Mitosis

This type of cell division occurs in somatic cells The mitotic cell division is a process whereby one cell divides into two daughter cells that are genetically identical to the parent cell Each daughter cell receives the com-plete complement of 46 chromosomes The period

between the two mitotic divisions is called interphase

During interphase, i.e., before mitosis begins, each chromosome replicates its deoxyribonucleic acid (DNA)

During this period, the chromosomes are in the form of long and thin threads (chromatin threads), which spread diffusely within the nucleus They cannot be recognized with a light microscope (Fig 3.1)

The various stages of mitosis are as follows (Fig 3.2):

1 Prophase: In this stage, nucleolus disappears The

chromosomes become coiled.* They condense, shorten, and thicken Each chromosome now con-sists of two parallel subunits called chromatids, which

remain joined to each other at a narrow common region called centromere But the chromatids cannot

be recognized

2 Prometaphase: In this stage, the chromatids

become distinguishable

3 Metaphase: In this stage, the nuclear membrane

breaks The double structured chromosomes (vide supra) line up in the equatorial plane of the spin-dle and get attached to the microtubules of the spindle extending between two centrioles, one at each pole

4 Anaphase: In this stage, the centromere of each

chromosome splits and the two chromatids are separated from each other They are now called

daughter chromosomes The spindle fibers attached to

the centromere, of the chromosomes contract and pull the daughter chromosomes towards poles

Due to pull on centromere, the daughter somes become V-shaped with their arms trailing as they move towards the poles

chromo-* Shortening of chromosomes by coiling reduces the chances of pinching off of the fragments of chromosomes.

Nuclear membrane

Nucleolus

Replication

of DNA Chromatin

threads

Fig 3.1 Cell in interphase: A Early interphase B Late interphase.

• Chromosome with two identical chromatids

• Chromatids are not recognized • Centrioles move to opposite poles• Chromatids become recognizable • Nuclear membrane disappears• Chromosomes line up on equator

• Are attached to the spindle fibers

furrow

Telophase Anaphase

Centromere

Spindle fibers Centriole

Fig 3.2 Various stages of mitosis.

5 Telophase: In this stage, the separated chromatids

are migrated to the opposite poles of the spindle

The spindle fibers disappear and nuclear

mem-brane appears around each polar group of

daugh-ter chromosomes The chromosomes uncoil and

become less compact The nucleolus reappears

There appears a cleavage furrow beneath the

equa-tor that deepens and separates the two daughter

cells (cytokinesis).

Significance of mitosis

1 Genetic stability: It ensures continuous succession of

identi-cal cells through generations.

2 Growth and development: It helps in growth and

develop-ment of the body.

3 Regeneration, replacement, and repair: It helps in

regenera-tion of new cells to replace the dead or damaged cells.

Clinical Correlation

Meiosis (Fig 3.3)

The meiosis is a special type of cell division that takes

place only in the reproductive organs to produce

gam-etes The meiosis consists of two phases of cell divisions

that take place one after the other (a) First meiotic

division (also known as reductional division): In this

the number of chromosomes of the daughter cells is

reduced to half of the mother cell (b) The second

mei-otic division: It is the mitmei-otic division similar to one

described above except that there is no duplication of DNA during short interphase

• Four chromatids become visible (tetrahed)

• Crossing over (synapsis

of two central chromatids)

• Formation of chiasmata

• Formation of spindles

• Homologous chromosomes get arranged on the equatorial plane

D Diplotene

E Diakinesis

C Pachytene

Metaphase

B Zygotene

A Leptotene

• Chromosomes after genetic exchange migrate towards the nuclear membrane

• One entire chromosome migrates to the opposite pole

• There is no splitting of chromosome

• Two daughter cells containing half the number of chromosomes (haploid number)

Second meiotic division after short interphase

• Formation of four daughter cells each with haploid number of chromosomes

Anaphase

Telophase

Fig 3.3 Meiotic division I and II: A, B, C, D, and E showing five stages of prophase of first meiotic division.

I First Meiotic Division

1 Prophase: Prophase of the first meiotic division is

very long and complicated It is therefore divided

into following five stages

(a) Leptotene: In this stage, the chromosomes, as

in mitosis, appear as slender threads Note:

Although each chromosome consists of two chromatids that are joined at centromere, the chromatids are not visible at this stage

(b) Zygotene: In this stage, the lengthwise pairing

of homologous chromosomes begins One of the two homologous chromosomes is from the

father (paternal chromosome) and the other

is from the mother (maternal chromosome)

This event is called synapsis and each ing pair is called bivalent.

synaps-(c) Pachytene: This stage is very long and may

extend even for years It is characterized by following changes

● The chromatids of each chromosome become visible separately Each bivalent chromo-some thus appears to have four chromatids

and is called tetrahed Each chromatid pair

is united by a kinetochore There are two

central chromatids and two peripheral matids (one from each chromosome)

chro-● The two central chromatids (one belonging

to each chromosome) of tetrahed, coil over each other so that they cross at a number of

points This is called crossing over Due to

crossing over the central chromatids present

a cross-like configuration called chiasmata.

(d) Diplotene: It is characterized by following

(e) Diakinesis: The chromosomes become more

contracted and migrate towards the nuclear membrane At the end of prophase, the nuclear membrane disappears

2 Metaphase: The homologous pairs of chromosomes

become arranged on the equatorial plane of the

spindle

3 Anaphase: In this stage, the homologous

chromo-somes migrate to the opposite poles of the spindle

Unlike mitosis the chromosomes move randomly

The shorter chromosomes move earlier than the

longer chromosomes

4 Telophase: This stage presents following features.

● The nuclear membrane is formed around the polarized group of chromosomes

● The cell membrane constricts and two daughter

cells are formed (cytokinesis) Each daughter

cell thus formed contains only half the number

of chromosomes (haploid number) with

exchanged genetic material

II Second Meiotic Division The second meiotic division is essentially similar to

mitosis It, however, differs from mitosis in that the DNA does not duplicate By second meiotic division, the two daughter cells of first meiotic division form four daughter cells, each with haploid number of chromosomes

Significance of meiosis

1 Sexual reproduction: As the chromosome number is reduced

to half during meiosis, each germ cell has haploid number of

chromosomes When two germ cells unite to form a zygote

the chromosome number is restored to normal (diploid ber of chromosomes) Thus, because of meiosis the chromo-

num-some number is maintained for the species.

2 Genetic variation: Because of random assortment of

pater-nal and materpater-nal chromosomes, and exchange of genetic material during crossing over in the meiosis, the daughter cells (i.e., gametes) have a new genetic configuration This causes individual variations within the species, which is essential for evolution.

3 Hybrid vigor: Helps to maintain vigor in progeny through

• Takes place in somatic cells • Takes place in germ cells

• Completes in one sequence • Completes in two sequences,

i.e., there are two successive

divisions, viz., meiosis I and

• Daughter cells have half the number of chromosomes as parent cells

• Daughter cells are identical

to each other and to the parent cell

• Daughter cells are not identical to each other and

to the parent cell

• Equational division • Reductional division

The spermatogenesis is the process of formation of

spermatozoa from primordial germ cells

(PGCs)/sper-matogonia present in the walls of the seminiferous

tubules of the testis

The PGCs remain dormant in the seminiferous

tubules of testes till puberty At puberty, they undergo

a series of divisions to form spermatogonia The various

stages of spermatogenesis are (Fig 3.4) as under:

1 The PGCs divide by mitosis to form dark type A

spermatogonia, which act as stem cells Each dark

type A spermatogonium undergoes mitosis to form

one dark A spermatogonium and other light type

A spermatogonium The dark type A

spermatogo-nia are kept in reserve for repetition of the next

cycle The light type A undergoes mitotic division

to form two dark type B spermatogonia

2 The type B spermatogonium undergoes mitotic

division to form two primary spermatocytes

(larg-est germ cells)

N.B Spermatocytogenesis: In this process, PGCs undergo a

series of mitotic divisions to form a large number of gonia Depending upon their appearance, three types of sper- matogonia are distinguished, viz., (a) dark type A spermatogonia, (b) light type A spermatogonia, and (c) type B spermatogonia.

3 The primary spermatocytes undergo first meiotic division (reductional division) to form two sec-

ondary spermatocytes The secondary

spermato-cytes thus have haploid number of chromosomes

4 Each secondary spermatocyte immediately goes second meiotic division (i.e., mitotic division)

under-to form two spermatids, each with haploid

Spermatogonium (Type B)

Primary spermatocyte (largest germ cell)

Second meiotic division

Second meiotic

division

44XY 44XY 44XY 44XY 44XY 44XY 44XY

PGC

Dark type A spermatogonium

Dark type A spermatogonium

Dark type A spermatogonium Light type A

spermatogonium

Type B spermatogonium

Type B spermatogonium Mitosis

Secondary spermatocytes

Spermiogenesis

Fig 3.4 Spermatogenesis (simplified form) Figure in the inset shows spermatocytogenesis.

of the secondary spermatocyte, and have round and darkly stained nuclei.

The spermatids lie close to the lumen of niferous tubule

5 Each spermatid gradually changes its stage to become spermatozoon or sperm This transforma-tion of circular spermatid into an elongated sper-

matozoon is called spermiogenesis.

Thus from one primary spermatocyte four spermatozoa are formed; two with 22 autosomes and one X chromo-some (22 + X, 22 + X) and two with 22 autosomes and one Y chromosomes (22 + Y, 22 + Y) (Fig 3.4)

The steps of spermatogenesis are summarized in Flowchart 3.1

To understand the process of spermiogenesis, the student must first understand the structure of sperma-tozoon (Fig 3.5)

Structure of Spermatozoon (Fig 3.5)

The spermatozoon (50 μ in length) consists of head, neck, and tail The tail is further divided into three parts: middle piece, principle piece, and end piece Tail forms four-fifth of the length

Primordial germ cell

Mitosis Spermatogonium (Type B)

Primary spermatocyte (44XY, 4nDNA)

Secondary spermatocyte (22X/Y, 2nDNA)

First Meiotic Division

Spermatid (22X/Y, nDNA)

Spermatid (22X/Y, nDNA)

SPERMIOGENESIS

Spermatozoon (22X/Y, nDNA)

Second Meiotic Division

Flowchart 3.1 Steps of spermatogenesis.

Head Neck

Middle piece

Principal piece

End piece

Tail

Cell membrane Acrosomal cap Nucleus

Proximal centriole Basal plate Cell membrane

Cell membrane Mitochondrial sheath Nine outer dense fibers Axial filament (cilium with 9+2 arrangement)

Cell membrane Fibrous sheath Seven outer dense fibers Axial filament

Cell membrane Axial filament

Parts of sperm Structure of different parts

Fig 3.5 Human sperm The parts of mature sperm are shown on the left side whereas the sections through the head, neck, middle

piece, principal piece, and end piece along with their composition are shown onto the right side.

Head The head of sperm appears somewhat like a

spearhead in section It mainly consists of a nucleus

that contains the condensed chromatin material (mostly

DNA) Anterior two-third of the nucleus is covered by

an acrosomal cap that contains various enzymes

including hyaluronidase and acrosin.

Neck The neck is narrow It contains a funnel-shaped

basal plate and a centriole The centriole gives rise to

axial filament that extends throughout the tail

Tail The tail consists of three parts: middle piece,

principal piece, and end piece

1 Middle piece: It contains the axial filament in

the  center that is surrounded by spirally

arranged  mitochondrial sheath At the distal

end of the middle piece there is a ring-like

struc-ture through which axial filament passes It is

called annulus and is derived from the other

centriole

2 Principle piece: It is made of axial filament

covered by seven outer dense fibers

3 End piece: It is made up of only the axial

filament

N.B.

• Structure of the axial filament is very similar to that of the

cilium.

• The whole sper matozoon is covered by plasma membrane

Figure 3.5 shows parts of the mature sperm (on the

left) and sections through head, neck, middle piece,

principal piece, and end piece along with their

compo-sition (on the right)

N.B The axial filament is responsible for the movements of

the spermatozoon, while mitochondria supply energy for these

movements.

Spermiogenesis

The process by which the spermatids are transformed

into mature spermatozoa is known as spermiogenesis

Process of Spermiogenesis (Fig 3.6)

The spermatid is more or less a circular cell containing

a nucleus, golgi apparatus, centrosome, and

mitochon-dria The spermatid is transformed into the

spermato-zoon as follows:

1 Nuclear material (chromatin) gets condensed and

the nucleus moves towards one pole of the cell to

form the head of the spermatozoon.

2 Golgi apparatus forms the acrosomal cap that

covers anterior two-third of the nucleus

3 Centrosome divides into two centrioles One triole becomes spherical and moves towards the posterior end of nucleus to occupy the neck region

cen-It gives rise to the axial filament The other

centriole moves away from the first centriole and

becomes ring shaped It forms an annulus/ring

around the distal end of the middle piece

through which axial filament passes

4 The part of the axial filament between the neck and annulus becomes surrounded by the mitochondria, and together with them forms the middle piece

5 The remaining part of the axial filament elongates

to form the principle and end pieces or tail Most

of the cytoplasm of spermatid is shed off but the cell membrane remains, which covers the entire spermatozoon

The structural components of the spermatid and the spermatozoon are compared in Table 3.2

Abnormal sperms: The abnormality of sperms is common as

compared to the oocytes Morphologically for clinicians the sperm consists of two parts of head and tail.

Types of abnormalities are as under.

2 Immotility: For potential fertility, 50% sperms should be

motile after 2 hours of ejaculation and some should be motile after 24 hours.

3 Genetic abnormalities: Sperm having abnormal

chromo-somal content (rare as compared to the oocytes).

Clinical Correlation

Oogenesis (Fig 3.7) The oogenesis is the process of formation of female

gametes—the oocytes from PGCs The process of oogenesis begins long before birth in the cortex of the ovary

The PGCs divide by mitosis to form a large number

of oogonia Each oogonium then enlarges to form a

pri-mary oocyte The pripri-mary oocyte enters the prophase

of first meiotic division before birth But this division

is arrested till puberty due to the presence of an oocyte

maturation inhibitor (OMI) factor secreted by the

fol-licular cells surrounding the oocyte The first meiotic division gets completed only when primary oocytes start maturing and are getting prepared for ovulation

At puberty in each ovarian cycle, 5–50 primary oocytes re-assume their first meiotic division, which is

completed just before the ovulation, forming two daughter cells each with haploid number of chromo-somes The first meiotic division is unequal; most of

the cytoplasm goes to one daughter cell forming

sec-ondary oocyte, while the other daughter cell receives

minimal cytoplasm and forms the first polar body.

The secondary oocyte enters the second meiotic

division at the time of ovulation, but this division is

completed only after the sperm has penetrated the ondary oocyte The second meiotic division is also unequal so that one daughter cell receives most of the cytoplasm and forms the ovum, while the other daugh-ter cell receives a very small amount of cytoplasm and

sec-forms the second polar body.

Thus, one primary oocyte forms only one ovum with

22 autosomes and one X chromosome; and three polar

Golgi apparatus Nucleus Mitochondrion Centrosome

Acrosomal cap

Head Neck

Spiral mitochondrial sheath

Fig 3.6 Process of spermiogenesis.

Table 3.2 Comparison of structural components of the

spermatid and the spermatozoon

Spermatid (round cell) Spermatozoon (elongated cell)

• Golgi apparatus • Acrosomal cap

• One centrosome • Two centrioles

(a) One lies in the neck and forms axial filament (b) Other forms annulus at the distal end of middle piece

• Mitochondria • Spirally surround the axial

filament between the neck and annulus to form the middle piece; the remaining axial filament forms the tail

• Cell membrane • Cell membrane